# Dissecting the Role of Radiation in Regulation of MHC-I and Neoantigen Presentation

> **NIH NIH F30** · DUKE UNIVERSITY · 2024 · $41,419

## Abstract

Abstract:
Immunotherapy has recently emerged as a promising new approach to cancer treatment. Durable anti-tumor
responses have been achieved with immune checkpoint inhibitors (ICIs) such as anti-PD1 and anti-CTLA4.
However, most cancer patients respond poorly to ICIs, including soft tissue sarcoma patients. An important
research objective in improving therapy for soft tissue sarcoma patients is to understand pathways that are
associated with resistance to ICIs. Downregulation of the antigen presentation pathway has been associated
with resistance to ICIs in various cancers. Radiation therapy, on the other hand, has been shown to increase
antigen presentation. Although it has been postulated that radiotherapy enhances therapeutic effects of ICIs
through upregulation of MHC-I molecules, the regulatory pathway(s) for radiation-induced MHC-I upregulation
remains poorly understood. To investigate the role of radiotherapy in modulating tumor antigen presentation, I
will use genetically engineered mouse models of autochthonous soft tissue sarcomas to dissect the
mechanisms responsible for modulating MHC-I expression after radiation.
The long-term goal of this project is to elucidate the mechanisms by which radiotherapy can help to overcome
immunotherapy resistance. The primary objective of this proposal is to investigate the underlying pathway
through which radiotherapy modulates the MHC-I antigen presentation pathway. The central hypothesis of this
study is that radiotherapy upregulates MHC-I expression in soft tissue sarcomas, which increases neoantigen
presentation to the immune system and sensitizes tumor cells to cytotoxic T cell killings and ICI treatments. I
will test this hypothesis in the following two specific aims:
Aim 1: Investigate regulatory networks responsible for MHC-I expression in soft tissue sarcomas.
Aim 2: Test whether radiation increases neoantigen presentation on tumor cells and antigen-presenting cells in
vivo.

## Key facts

- **NIH application ID:** 10751000
- **Project number:** 5F30CA268910-03
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Chang Su
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $41,419
- **Award type:** 5
- **Project period:** 2021-12-02 → 2025-12-02

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10751000

## Citation

> US National Institutes of Health, RePORTER application 10751000, Dissecting the Role of Radiation in Regulation of MHC-I and Neoantigen Presentation (5F30CA268910-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10751000. Licensed CC0.

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